The effect of intrathecal delivery of bone marrow stromal cells on hippocampal neurons in rat model of Alzheimer's disease.

OBJECTIVES: Intracerebral injection of bone marrow stromal cells (BMSCs) is being investigated as a therapeutic tool to prevent Alzheimer's disease (AD). Our aim was to investigate the effects of BMSCs by intrathecal injection in AD rat model. MATERIALS AND METHODS: BMSCs were obtained from the bone marrow of Wistar rat and transplanted into AD rat model via intrathecal injection. The rat model had received an injection of β amyloid into the hippocampus for histological and immunohistochemical studies. RESULTS: Histological examination of the brains in transplanted rats compared to controls demonstrated the migration of BrdU-labeled BMSCs from the site of delivery, confirmed the differentiation of BMSCs transplanted cells into the cholinergic neurons, and increased number of healthy and decreased number of dark neurons. CONCLUSION: Our results showed that BMSCs intratechal administration could be a promising method for treatment of Alzheimer's disease in rat model

Flow cytometric analysis for apoptosis of fibroblasts.

<p>Representative dot plots of the flow cytometric analysis of the Annexin V–FITC/propidium iodide (PI) following induction of apoptosis with H₂O₂. Fibroblasts derived from SM-exposed patients and controls were assessed for spontaneous apoptosis and apoptosis following treatment with 500, 700 and 900 μM of H₂O₂. Spontaneous apoptosis was not significantly different in SM-exposed patients and controls. However, a higher dose-dependent sensitivity to H₂O₂ is observed in patients as compared with controls. Q₁: necrotic cells, Q₂: late apoptotic cells, Q₃: viable cells, and Q₄: early apoptotic cells.</p

Immunocytochemical detection of α-SMA and fibronectin expression.

<p>Both SM-exposed patients and controls expressed α-SMA (A and B, 10×) and fibronectin (C and D, 20×). The number of positive cells was determined by enumeration of 100 cells/sample. Figures E and F present the count of positive cells as mean ± SEM for patients (n = 5) and controls (n = 4). *p < 0.0001. Arrows show positive cells; Abbreviations: α-SMA alpha smooth muscle actin, SM sulfur mustard.</p

Cell migration.

<p>The migration distance of fibroblasts isolated from SM-exposed patients (n = 5) was significantly higher than the distance migrated by controls (n = 4); *p < 0.05. Abbreviations: SM sulfur mustard.</p

Immunocytochemical characterization of fibroblasts.

<p>The cells from both SM-exposed patients and controls were negative for pancytokeratin staining (A and B; 10×) and positive for vimentin (C and D; 10×).</p

Population doubling levels (PDLs).

<p>PDLs of SM-exposed patients and controls were compared at each passage performed at different time points after the start of the primary culture. Each individual culture's PDL was presented by a red dot. PDL of the SM-exposed patients were significantly higher than controls from the day 7 through 28, but did not show any significant difference on the day 35. * p = 0.0025, ** p = 0.0001, *** p < 0.05.</p